The Australian registry of anti-epileptic drugs in pregnancy: experience after 30 months.

BACKGROUND: Most women with epilepsy need to take antiepileptic drugs (AEDs) in pregnancy to prevent the potentially harmful effects of seizures. Retrospective studies have demonstrated an increased chance of having a child with a birth defect (BD) in women with epilepsy taking AEDs. It is uncertain how much of this risk is directly caused by the AEDs and whether certain drugs or combinations are associated with a greater risk. AIMS: To establish a register to evaluate prospectively the incidence of adverse pregnancy outcomes in women exposed to specific AEDs; to determine whether certain AEDs or combinations were associated with a greater risk; and to determine whether other factors influenced the risk. METHODS: An Australia-wide, prospective, voluntary, telephone-interview based, observational register. Three groups of pregnant women were enrolled: those with epilepsy taking AEDs, those with epilepsy not taking AEDs, and those taking AEDs for a non-epileptic indication. The pregnancy outcomes were evaluated by follow-up interviews and by reference to hospital and treating doctors' records. RESULTS: Over the first 30 months of the study (till December 2001) 334 eligible women were enrolled, with all states and territories being represented. Two hundred and ninety two pregnancies had been completed, of which 256 (88%) resulted in a healthy live birth, 19 (6.5%) a live birth with a birth defect, four an induced abortion because of a detected malformation on ultrasound, one premature labour with a stillbirth and 12 (4%) spontaneous abortions. Of the completed pregnancies, 269 were exposed to at least one AED during the first trimester. The incidence of birth defects in relation to specific AEDs was: valproate (16.7%), phenytoin (10.5%), lamotrigine (7.7%) and carbamazepine (3.3%), none of which was significantly different from that in women with epilepsy not taking an AED (4.3%, n.s.). The dose of valproate taken was higher in pregnancies with BD compared to those without (mean 2081 mg vs. 1149 mg, p<0.0001). The incidence of folate supplementation being taken prior to conception did not differ for pregnancy outcomes with or without BD (70% vs. 66%, n.s.). CONCLUSIONS: The model for the Australian Pregnancy Register appears to be successful, with strong enrolment from all regions over the first 30 months. The study is prospective and includes reference to all new AEDs approved in Australia over the past decade. Analysis of the pregnancy outcomes to date may reveal early trends, but numbers are still to small for any definitive conclusions to be made regarding the relative risk in pregnancy of individual AEDs.     

Attenuated adrenergic responses to exercise in women with fibromyalgia – A controlled study

The pathogenesis of widespread pain and fibromyalgia (FM) is unknown. Altered responses from the hypothalamus–pituitary–adrenal axis, sympathetic nervous system and muscular system have been suggested as being of importance. The present study was undertaken to determine: (i) whether the sympathoadrenal response to repetitive isometric contractions until exhaustion is altered in patients with FM, and (ii) whether sympathoadrenal responses are associated with muscle fatigue and pain during exercise. Nineteen women with FM, and 19 healthy women matched for age, smoking and self‐reported physical activity, participated. Maximal voluntary contraction (MVC), repetitive isometric contractions (6s contraction and 4s resting phases) were performed with both quadriceps muscles at 30% of MVC until exhaustion. Muscle activity was recorded from the quadriceps muscles by surface electromyography (EMG). Plasma adrenalin (Adr), noradrenalin (NAdr) and cortisol were measured and perceived exertion and pain reported during exercise. Attenuated Adr responses (p<0.001) with normal plasma NAdr and cortisol (p>0.19) responses were found during exercise in the FM group compared with the control group. Significantly higher EMG amplitude (%EMG_max) during the contraction phases (p=0.001) was found in the FM than in the control group. Perceived exertion and pain responses to exercise were higher in the FM group than in the controls (p<0.001), without relationship to the sympathoadrenal responses. In conclusion; the exercise was perceived as being more painful and strenuous in the FM group. Muscle performance was altered with increased muscle activity during the exercise. Women with FM showed an attenuated Adr response to repetitive isometric exercise.     

The heat shock response of Fusobacterium nucleatum

The heat-shock response of the oral Gram-negative bacterium Fusobacterium nucleatum was examined. Different strains of F. nucleatum were grown at 37 C. 42 degrees C and 48 C in the presence of [35S]methionine. Cellular proteins synthesised after shifts to higher temperatures were analysed by SDS-PAGE and autoradiography. Strains ATCC 10953, F1, F3 and Fev1 exhibited heat-shock response, and major proteins were observed at 60, 70 and 90 kDa. but increased protein synthesis was also observed for other proteins. Immunoblot analysis, using a panel of antibodies directed to epitopes on different known heat-shock proteins revealed cross-reactive proteins, indicating homology between Escherichia coli, Mycobacterium leprae and F. nucleatum heat shock proteins.     

The internal control group in a register of antiepileptic drug use in pregnancy.

The aim of this study was to determine how valid 68 first-trimester pregnancies of untreated epileptic women would prove as an internal control group for investigating foetal malformation rates in 709 simultaneously collected antiepileptic drug-exposed pregnancies in an Australian register of pregnancies in epileptic women. We carried out comparisons of values for parameters relating to personal details, obstetric aspects, and epilepsies prior to and during pregnancy in the drug-exposed and drug-unexposed pregnancies, with observations on subpopulations within the drug-unexposed group. Statistically significant (p<0.05) differences existed for only seven of more than 50 parameters compared. None of these seven parameters had a statistically significant influence on foetal malformation rates in the whole dataset. In 23 of the 65 epileptic pregnancies unexposed to antiepileptic drugs, therapy had been ceased shortly prior to pregnancy and was often resumed after the first trimester. In the remaining 42, therapy had been ceased earlier, often despite continuing seizures. Planned withdrawal of therapy did not appear to produce additional hazards for mothers and foetuses in the former subgroup. In the data collection studied, there did not appear to be evidence of statistically significant differences between untreated pregnancies and treated epileptic pregnancies that would be likely to invalidate the former group as an internal control for the latter, at least when assessing foetal malformation rates.